Normative structural MRI deviation factors summarize patient-level neuroanatomical heterogeneity across episodic and chronic migraine

Structural MRI findings in migraine are inconsistent across cohorts, suggesting that group contrasts may obscure patient-level heterogeneity. We tested whether individualized normative structural deviations could be summarized into interpretable patient-level factor-weight dimensions related to chronicity and clinical burden. In this single-center cross-sectional study, 249 adults with ICHD-3 migraine (198 episodic, 51 chronic) and 57 local healthy controls underwent 3.0-T MRI. Released PCNtoolkit lifespan models were locally adapted with controls to estimate patient-level deviation z scores for 158 FreeSurfer features. Non-negative matrix factorization was applied to the absolute-deviation matrix; directional negative- and positive-deviation models were sensitivity analyses. Covariate-adjusted associations were FDR-corrected within prespecified families. The primary model identified two stable factor-weight dimensions. Factor 1 captured a subcortical-limbic-brainstem/global-volume deviation pattern and was associated with chronic migraine (OR per 1-SD, 1.50; q = 0.036), MIDAS (beta = 16.46; q = 0.007), and monthly headache days (beta = 9.41; q < 0.001). Factor 2 mainly reflected cortical-thickness deviations, showed a borderline inverse association with chronic migraine (OR = 0.68; q = 0.054), and was associated with high absolute-deviation burden (OR = 2.37; q < 0.001). HIT-6 showed no corrected factor-specific association. Removing cranial-size-sensitive features preserved factor structure and main Factor 1 associations. Normative structural MRI deviations in migraine can be summarized into non-mutually exclusive deviation-burden factors with patient-level weights. Factor 1 showed the most consistent associations with chronic migraine, headache frequency, and MIDAS; these associations attenuated in restricted sensitivity analyses, and external validation is required before clinical application.